ID   FEM1A_HUMAN             Reviewed;         669 AA.
AC   Q9BSK4; B2RDI3; Q711P8; Q9NPN7; Q9NPW8;
DT   18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   07-OCT-2020, entry version 169.
DE   RecName: Full=Protein fem-1 homolog A;
DE            Short=FEM1a;
DE   AltName: Full=FEM1-alpha;
DE   AltName: Full=Prostaglandin E receptor 4-associated protein;
GN   Name=FEM1A; Synonyms=EPRAP;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INTERACTION WITH
RP   PTGER4.
RX   PubMed=16424369; DOI=10.1161/01.res.0000204451.88147.96;
RA   Takayama K., Sukhova G.K., Chin M.T., Libby P.;
RT   "A novel prostaglandin E receptor 4-associated protein participates in
RT   antiinflammatory signaling.";
RL   Circ. Res. 98:499-504(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-669.
RC   TISSUE=Skeletal muscle;
RA   Ievolella C., Zara I., Millino C., Faulkner G., Lanfranchi G.;
RT   "Full length sequencing of an human and murine muscular transcripts
RT   (Telethon Italy project B41).";
RL   Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 470-669.
RG   The European IMAGE consortium;
RL   Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 576-669.
RC   TISSUE=Melanoma;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [7]
RP   INDUCTION.
RX   PubMed=16254458; DOI=10.1159/000089261;
RA   Ventura-Holman T., Hahn H., Subauste J.S., Maher J.F.;
RT   "The Fem1a gene is downregulated in Rhabdomyosarcoma.";
RL   Tumor Biol. 26:294-299(2005).
RN   [8]
RP   VARIANT TYR-500.
RX   PubMed=16390781; DOI=10.1080/09513590500431458;
RA   Maher J.F., Hines R.S., Futterweit W., Crawford S., Lu D., Shen P.,
RA   Oefner P., Kazi M., Wilson J.G., Subauste J.S., Cowan B.D.;
RT   "FEM1A is a candidate gene for polycystic ovary syndrome.";
RL   Gynecol. Endocrinol. 21:330-335(2005).
CC   -!- FUNCTION: Probable component of an E3 ubiquitin-protein ligase complex,
CC       in which it may act as a substrate recognition subunit (By similarity).
CC       May participate in antiinflammatory signaling via its interaction with
CC       PTGER4. {ECO:0000250}.
CC   -!- PATHWAY: Protein modification; protein ubiquitination.
CC   -!- SUBUNIT: Component of some E3 ubiquitin-protein ligase complex (By
CC       similarity). Interacts with PTGER4. {ECO:0000250,
CC       ECO:0000269|PubMed:16424369}.
CC   -!- INTERACTION:
CC       Q9BSK4; P09110: ACAA1; NbExp=3; IntAct=EBI-2515349, EBI-3926709;
CC       Q9BSK4; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-2515349, EBI-5916454;
CC       Q9BSK4; Q0VD86: INCA1; NbExp=3; IntAct=EBI-2515349, EBI-6509505;
CC       Q9BSK4; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-2515349, EBI-14069005;
CC       Q9BSK4; Q9UDY8-2: MALT1; NbExp=3; IntAct=EBI-2515349, EBI-12056869;
CC       Q9BSK4; Q5VTT5-2: MYOM3; NbExp=3; IntAct=EBI-2515349, EBI-12247808;
CC       Q9BSK4; O14561: NDUFAB1; NbExp=3; IntAct=EBI-2515349, EBI-1246261;
CC       Q9BSK4; Q8N543: OGFOD1; NbExp=3; IntAct=EBI-2515349, EBI-13327083;
CC       Q9BSK4; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-2515349, EBI-12040603;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Present in macrophages derived from peripheral
CC       blood monocytes. Also present in atheromata (at protein level).
CC       {ECO:0000269|PubMed:16424369}.
CC   -!- INDUCTION: Frequently down-regulated in rhabdomyosarcoma.
CC       {ECO:0000269|PubMed:16254458}.
CC   -!- SIMILARITY: Belongs to the fem-1 family. {ECO:0000305}.
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DR   EMBL; AY356352; AAR10439.1; -; mRNA.
DR   EMBL; AK315554; BAG37930.1; -; mRNA.
DR   EMBL; BC004988; AAH04988.1; -; mRNA.
DR   EMBL; AJ311359; CAC85342.1; -; mRNA.
DR   EMBL; AL365408; CAB96952.1; -; mRNA.
DR   EMBL; AL359589; CAB94875.1; -; mRNA.
DR   EMBL; CR749732; CAH18491.1; -; mRNA.
DR   CCDS; CCDS12135.1; -.
DR   PIR; T50619; T50619.
DR   RefSeq; NP_061178.1; NM_018708.2.
DR   SMR; Q9BSK4; -.
DR   BioGRID; 120699; 25.
DR   IntAct; Q9BSK4; 20.
DR   STRING; 9606.ENSP00000269856; -.
DR   iPTMnet; Q9BSK4; -.
DR   PhosphoSitePlus; Q9BSK4; -.
DR   BioMuta; FEM1A; -.
DR   DMDM; 74752305; -.
DR   EPD; Q9BSK4; -.
DR   jPOST; Q9BSK4; -.
DR   MassIVE; Q9BSK4; -.
DR   MaxQB; Q9BSK4; -.
DR   PaxDb; Q9BSK4; -.
DR   PeptideAtlas; Q9BSK4; -.
DR   PRIDE; Q9BSK4; -.
DR   ProteomicsDB; 78912; -.
DR   Antibodypedia; 11533; 140 antibodies.
DR   DNASU; 55527; -.
DR   Ensembl; ENST00000269856; ENSP00000269856; ENSG00000141965.
DR   GeneID; 55527; -.
DR   KEGG; hsa:55527; -.
DR   UCSC; uc002mbf.4; human.
DR   CTD; 55527; -.
DR   DisGeNET; 55527; -.
DR   EuPathDB; HostDB:ENSG00000141965.4; -.
DR   GeneCards; FEM1A; -.
DR   HGNC; HGNC:16934; FEM1A.
DR   HPA; ENSG00000141965; Tissue enriched (skeletal).
DR   MIM; 613538; gene.
DR   neXtProt; NX_Q9BSK4; -.
DR   OpenTargets; ENSG00000141965; -.
DR   PharmGKB; PA134940973; -.
DR   eggNOG; KOG0508; Eukaryota.
DR   GeneTree; ENSGT00940000161210; -.
DR   HOGENOM; CLU_020042_2_0_1; -.
DR   InParanoid; Q9BSK4; -.
DR   OMA; DHCGARV; -.
DR   OrthoDB; 252380at2759; -.
DR   PhylomeDB; Q9BSK4; -.
DR   TreeFam; TF351376; -.
DR   PathwayCommons; Q9BSK4; -.
DR   Reactome; R-HSA-8951664; Neddylation.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 55527; 30 hits in 851 CRISPR screens.
DR   ChiTaRS; FEM1A; human.
DR   GenomeRNAi; 55527; -.
DR   Pharos; Q9BSK4; Tbio.
DR   PRO; PR:Q9BSK4; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q9BSK4; protein.
DR   Bgee; ENSG00000141965; Expressed in skeletal muscle tissue and 214 other tissues.
DR   Genevisible; Q9BSK4; HS.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0000151; C:ubiquitin ligase complex; IBA:GO_Central.
DR   GO; GO:0031867; F:EP4 subtype prostaglandin E2 receptor binding; IPI:UniProtKB.
DR   GO; GO:0050728; P:negative regulation of inflammatory response; IDA:UniProtKB.
DR   GO; GO:0043687; P:post-translational protein modification; TAS:Reactome.
DR   GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR   GO; GO:0051438; P:regulation of ubiquitin-protein transferase activity; ISS:UniProtKB.
DR   GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR   Gene3D; 1.25.40.10; -; 1.
DR   Gene3D; 1.25.40.20; -; 3.
DR   InterPro; IPR002110; Ankyrin_rpt.
DR   InterPro; IPR020683; Ankyrin_rpt-contain_dom.
DR   InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR   InterPro; IPR011990; TPR-like_helical_dom_sf.
DR   Pfam; PF12796; Ank_2; 4.
DR   PRINTS; PR01415; ANKYRIN.
DR   SMART; SM00248; ANK; 9.
DR   SUPFAM; SSF48403; SSF48403; 2.
DR   SUPFAM; SSF48452; SSF48452; 1.
DR   PROSITE; PS50297; ANK_REP_REGION; 2.
DR   PROSITE; PS50088; ANK_REPEAT; 7.
PE   1: Evidence at protein level;
KW   ANK repeat; Cytoplasm; Polymorphism; Reference proteome; Repeat;
KW   TPR repeat; Ubl conjugation pathway.
FT   CHAIN           1..669
FT                   /note="Protein fem-1 homolog A"
FT                   /id="PRO_0000324525"
FT   REPEAT          2..31
FT                   /note="ANK 1"
FT   REPEAT          40..70
FT                   /note="ANK 2"
FT   REPEAT          82..111
FT                   /note="ANK 3"
FT   REPEAT          115..145
FT                   /note="ANK 4"
FT   REPEAT          149..178
FT                   /note="ANK 5"
FT   REPEAT          182..211
FT                   /note="ANK 6"
FT   REPEAT          214..243
FT                   /note="ANK 7"
FT   REPEAT          298..332
FT                   /note="TPR 1"
FT   REPEAT          390..423
FT                   /note="TPR 2"
FT   REPEAT          534..576
FT                   /note="ANK 8"
FT   REPEAT          580..609
FT                   /note="ANK 9"
FT   VARIANT         500
FT                   /note="H -> Y (found in a patient with polycystic ovary
FT                   syndrome; unknown pathological significance)"
FT                   /evidence="ECO:0000269|PubMed:16390781"
FT                   /id="VAR_039809"
SQ   SEQUENCE   669 AA;  73639 MW;  FF0010DE5207D48F CRC64;
     MDLRTAVYNA ARDGKLQLLQ KLLSGRSREE LDELTGEVAG GGTPLLIAAR YGHLDVVEYL
     VDRCGASVEA GGSVHFDGET IEGAPPLWAA SAAGHLDVVR SLLRRGASVN RTTRTNSTPL
     RAACFDGHLE VVRYLVGEHQ ADLEVANRHG HTCLMISCYK GHREIARYLL EQGAQVNRRS
     AKGNTALHDC AESGSLEILQ LLLGCKARME RDGYGMTPLL AASVTGHTNI VEYLIQEQPG
     QEQVAGGEAQ PGLPQEDPST SQGCAQPQGA PCCSSSPEEP LNGESYESCC PTSREAAVEA
     LELLGATYVD KKRDLLGALK HWRRAMELRH QGGEYLPKPE PPQLVLAYDY SREVNTTEEL
     EALITDPDEM RMQALLIRER ILGPSHPDTS YYIRYRGAVY ADSGNFERCI RLWKYALDMQ
     QSNLEPLSPM TASSFLSFAE LFSYVLQDRA AKGSLGTQIG FADLMGVLTK GVREVERALQ
     LPREPGDSAQ FTKALAIILH LLYLLEKVEC TPSQEHLKHQ TVYRLLKCAP RGKNGFTPLH
     MAVDKDTTNV GRYPVGRFPS LHVVKVLLDC GADPDSRDFD NNTPLHIAAQ NNCPAIMNAL
     IEAGAHMDAT NAFKKTAYEL LDEKLLARGT MQPFNYVTLQ CLAARALDKN KIPYKGFIPE
     DLEAFIELH
//